This program is designed to explore in the individual patient the parameters of response to established chemotherapeutic agents and with newer antitumor agents to develop the basic pharmacological information preparatory to exploring such predictive parameters. In acute myelocytic leukemia the parameters being evaluated are the uptake and activation of ara-C in the leukemic myeloblast from the patients' bone marrow and retention of the active metabolite within the myeloblast in vitro and the drug uptake and specific DNA damage caused by incubation of the patients' myeloblasts with adriamycin and other anthracycline antibiotics. In the area of solid tumors malignant melanoma and lung tumors are beng subjected to a variety of disaggregation procedures both mechanical and enzymatic to optimize the formation of single cell suspensions of viable tumor cells. These cells are then used for enzymatic studies for measurement of nucleotide pools for nucleic acid precursor incorporation studies and for studies of the inhibition of precursor incorporation. In the area of newer antitumor agents a variety of agents are in different stages of development in the program. 3-Deazauridine has completed phase I studies and human pharmacokinetic studies and drug uptake studies in human myeloblast have been completed, while 2,4-diamino-5-adamantyl 6-methylpyrimidine (DAMP) dichloro-dihydroxy bis-isopropylamine platinum IV (CHIP) and 3-deazaguanine are under intensive preclinical investigation and preparation for their introduction into the clinic. In the coming year, it is proposed to investigate the integration of pharmacokinetic parameters with pharmacodynamic and biochemical pharmacological parameters of adriamycin and cytosine arabinoside in patients with acute myeloblastic leukemia, to extend these studies to other types of leukemia and to start investigation of such integrated parameters in patients with solid tumors. The program thus constitutes a comprehensive integrated approach to the determination of the parameters of response both to established antitumor agents and to investigational agents in both the leukemias and solid tumors.